title: The impact of specific and non-specific immunity on the ecology of Streptococcus pneumoniae and the implications for vaccination.
abstract: More than 90 capsular serotypes of Streptococcus pneumoniae coexist despite competing for nasopharyngeal carriage and a gradient in fitness. The underlying mechanisms for this are poorly understood and make assessment of the likely population impact of vaccination challenging. We use an individual-based simulation model to generalize widely used deterministic models for pneumococcal competition and show that in these models short-term serotype-specific and serotype non-specific immunity could constitute the mechanism governing between-host competition and coexistence. We find that non-specific immunity induces between-host competition and that serotype-specific immunity limits a type's competitive advantage and allows stable coexistence of multiple serotypes. Serotypes carried at low prevalence show high variance in carriage levels, which would result in apparent outbreaks if they were highly pathogenic. Vaccination against few serotypes can lead to elimination of the vaccine types and induces replacement by others. However, in simulations where the elimination of the targeted types is achieved only by a combination of vaccine effects and the competitive pressure of the non-vaccine types, a universal vaccine with similar-type-specific effectiveness can fail to eliminate pneumococcal carriage and offers limited herd immunity. Hence, if vaccine effects are insufficient to control the majority of serotypes at the same time, then exploiting the competitive pressure by selective vaccination can help control the most pathogenic serotypes.
authors.affiliation: Immunisation, Hepatitis and Blood Safety Department, Public Health England, , 61 Colindale Avenue, Colindale, London NW9 5EQ, UK, Department of Mathematics and Statistics, Strathclyde University, , 26 Richmond Street, Glasgow G1 1XH, UK, Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, , Keppel Street, London WC1E 7HT, UK, Institute of Child Health, University College London, , 30 Guilford Street, London WC1N 1EH, UK, Health Protection Scotland, , 5 Cadogan Street, Glasgow G2 6QE, UK, International Prevention Research Institute, , 95 Cours Lafayette, Lyon 69006, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Flasche
authors.forename: W John
authors.initials: WJ
authors.lastname: Edmunds
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
authors.forename: David
authors.initials: D
authors.lastname: Goldblatt
authors.forename: Chris
authors.initials: C
authors.lastname: Robertson
authors.forename: Yoon Hong
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000367:Age Factors; D003198:Computer Simulation; D006801:Humans; D056265:Microbial Interactions / Q000276:immunology*; D008954:Models, Biological; D009305:Nasopharynx / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000635:transmission*; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity; D006113:United Kingdom; D014611:Vaccination / Q000379:methods*
keywords: Streptococcus pneumoniae; carriage; coexistence; competition; immunity; vaccination